Differential kinetics of splenic CD169+ macrophage death is one underlying cause of virus infection fate regulation
Casella, Valentina (Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida)
Domenjo-Vila, Eva (Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida)
Esteve-Codina, Anna (Universitat Pompeu Fabra)
Pedragosa, Mireia (Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida)
Cebollada Rica, Paula (Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida)
Vidal Barba, Enric (Unitat mixta d'investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal)
de la Rubia, Ivan (Australia Partner Laboratory Network at the Australian National University)
López-Rodríguez, Cristina (Universitat Pompeu Fabra. Departament de Medicina i Ciències de la Vida)
Bocharov, Gennady (Sechenov First Moscow State Medical University)
Argilaguet, Jordi 1977- (Unitat mixta d'investigació IRTA-UAB en Sanitat Animal. Centre de Recerca en Sanitat Animal)
Meyerhans, Andreas (Institució Catalana de Recerca i Estudis Avançats)

Date:	2023
Abstract:	Acute infection and chronic infection are the two most common fates of pathogenic virus infections. While several factors that contribute to these fates are described, the critical control points and the mechanisms that underlie infection fate regulation are incompletely understood. Using the acute and chronic lymphocytic choriomeningitis virus (LCMV) infection model of mice, we find that the early dynamic pattern of the IFN-I response is a differentiating trait between both infection fates. Acute-infected mice generate a 2-wave IFN-I response while chronic-infected mice generate only a 1-wave response. The underlying cause is a temporal difference in CD8 T cell-mediated killing of splenic marginal zone CD169+ macrophages. It occurs later in acute infection and thus enables CD169+ marginal zone macrophages to produce the 2nd IFN-I wave. This is required for subsequent immune events including induction of inflammatory macrophages, generation of effector CD8+ T cells and virus clearance. Importantly, these benefits come at a cost for the host in the form of spleen fibrosis. Due to an earlier marginal zone destruction, these ordered immune events are deregulated in chronic infection. Our findings demonstrate the critical importance of kinetically well-coordinated sequential immune events for acute infection control and highlights that it may come at a cost for the host organism.
Grants:	Ministerio de Economía y Competitividad CEX2018-000792-M Instituto de Salud Carlos III PT17/0009/0019
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Viral infection ; Cell death and immune response ; Immune cell death ; Imaging the immune system
Published in:	Cell death and disease, Vol. 14 (december 2023) , ISSN 2041-4889

DOI: 10.1038/s41419-023-06374-y
PMID: 38110339

13 p, 6.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Centre de Recerca en Sanitat Animal (CReSA-IRTA)
Articles > Research articles
Articles > Published articles